Nt mutation causing laterality defects associated with deletion of rotatin

Area of Science:

• Developmental Biology
• Genetics
• Mouse Models

Background:

• The
• no turning
• (nt) mutation in mice leads to embryonic lethality by E11.5, characterized by left-right and axial patterning defects, including randomized heart tube looping and failure of embryonic turning.
• Previous research linked these defects to notochordal abnormalities and altered expression of key developmental genes like HNF3beta, lefty, and nodal.

Purpose of the Study:

• To identify the specific genetic cause of the
• no turning
• (nt) mutation.

Main Methods:

• Genetic mapping of the nt mutation in a Mus musculus castaneus background using polymorphic microsatellite DNA markers.
• Whole-genome scanning to localize the mutation to a specific interval on mouse chromosome 18.
• RT-PCR and chromosome walking to analyze gene expression and identify deletions within the mapped region.

Main Results:

• The nt mutation was mapped to an 18-Mb interval on mouse chromosome 18.
• A 1.6-Mb deletion encompassing four genes (Rttn, CD226, Dok6, and Txndc10) was identified in homozygous nt mutant embryos.
• A previously generated RTTN gene-trap mutant mouse line exhibited similar developmental defects to nt mutants.

Conclusions:

• The findings strongly suggest that deficiency of the RTTN gene is the underlying cause of the "no turning" mutation and its associated embryonic patterning defects.